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Human Leukocyte Antigen-G Protein Expression Is an Unfavorable Prognostic Predictor of Hepatocellular Carcinoma following Curative Resection
Ist Teil von
Clinical cancer research, 2009-07, Vol.15 (14), p.4686-4693
Ort / Verlag
Philadelphia, PA: American Association for Cancer Research
Erscheinungsjahr
2009
Quelle
MEDLINE
Beschreibungen/Notizen
Purpose: Human leukocyte antigen-G (HLA-G) is a tumor-associated immunosuppressive molecule involved in tumor escape mechanisms. The
aim of this study is to elucidate its prognostic significance in hepatocellular carcinoma (HCC).
Experimental Design: Immunohistochemical staining of HLA-G expression as well as tumor-infiltrating FoxP3 + regulatory (Tregs) and CD8 + cytotoxic T cells was carried out on tissue microarrays containing 173 HCC tissue specimens. Membrane-bound HLA-G1 protein
expression in five human HCC cell lines was detected by Western blot.
Results: HLA-G expression was associated with HCC prognosis, especially in early-stage diseases, with high expression independently
associated with shortened overall survival ( P = 0.041) and increased tumor recurrence ( P = 0.023). HLA-G level was positively related to Tregs/CD8 + ratio and their combination served as a better prognosticator, patients having concurrent high levels of both variables at
more than three times of risk of death and tumor relapse than those with concurrent low levels (both P < 0.001). In addition, HLA-G1 expression increased in a concordant manner with the increase of metastatic potential in human
HCC cell lines.
Conclusions: Overexpression of HLA-G protein in HCC was an independent indicator for poor outcome especially in early-stage disease. The
combination of HLA-G expression and Tregs/CD8 + ratio added the prognostic power to both variables, offering a possible strategy of tumor-stroma interaction-oriented cancer
immunotherapy.